More Stories From The Genetics Clinic

Question 1

What is genomic imprinting?

Answer 1

epigenetic modification of the genome that affects gene expression with no actual change in DNA sequence and is hereditary

Question 2

What is DNA methylation?

Answer 2

addition of methyl group to 5’ position of cytosine at CpG dinucleotides that is retained from parents to offspring

Question 3

What does DNA methylation do?

Answer 3

blocks access for TF and underlies imprinting

Question 4

What is maternal imprinting?

Answer 4

the gene is inactive if inherited from mother

Question 5

Name two Chromosome 15 imprinting disorders

Answer 5

prader-willi syndrome = paternal allele

angelman syndrome = maternal allele

Question 6

What is heteroplasty?

Answer 6

in mitochondrial disorders there is a different number of mitochondria in each cell so distinct population with different genomes so can affect different proportion of mitochondria

Question 7

What are the characteristics of MELAS?

Answer 7

mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes
progressive neurological disorder
fatal

Question 8

What are the gene mutations in MELAS?

Answer 8

single mutation in several genes

• tRNA translates Phe not Leu in mitochondrial protein synthesis = MTTL1
• NADH dehydrogenase subunits 1 + 5 = MTND1/5

Question 9

What are MELAS diagnosis and symptoms?

Answer 9

muscle biopsy

symptoms - vomiting, muscle weakness, seizure, headaches, dementia

Question 10

What are LHON characteristics?

Answer 10

Leber’s Hereditary Optic Neuropathy
more common in males
degeneration of retinal ganglion cells

Question 11

What are the gene mutations in LHON?

Answer 11

• cytochrome B = MTCYB

- NADH dehydrogenase subunits 1 + 5 = MTND1/4/5/6

Question 12

What are LHON symptoms?

Answer 12

bilateral painless vision loss, optic atrophy, blindness

Question 13

Name 2 methods to prevent mitochondrial diseases

Answer 13

3 parent babies, UK newborn screening

Question 14

What is included in a newborn screening?

Answer 14

physical exam, hearing test, blood test

Question 15

What are 2 conditions tested for in screening?

Answer 15

Phenylketonuria and Medium-chain Acyl-CoA Dehydrogenase

Question 16

What are characteristics of PKU?

Answer 16

phenylalanine hydroxylase deficiency

more than 600 mutations so test for metabolic consequences not mutation

Question 17

List PKU symptoms

Answer 17

lack of melanin, eczema, seizures, mental retardation due to build up of phenylalanine

Question 18

List PKU treatment

Answer 18

diet managed to remove phenylalanine
protein supplements
strict pregnancy diet

Question 19

What are characteristics of MCAD

Answer 19

fatty acid oxidation disorder

mutation of ACADM gene

Question 20

List MCAD symptoms

Answer 20

episodic hypoketotic hypoglycaemia, vomiting, coma, death, encephalopathy

Question 21

List MCAD treatment

Answer 21

avoid fasting as can’t convert fatty acids to acetyl CoA so no E store when used up glycogen
nutritional supplements